p.R209H GH1 variant challenges short stature assessment

Objective: to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive. Design: We describe a non-consanguineous pedigree composed by several individuals with...

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Detalhes bibliográficos
Autores: Sanguineti, Nora María, Braslavsky, Debora Giselle, Scaglia, Paula Alejandra, Keselman, Ana Claudia, Ballerini, Maria Gabriela, Ropelato, Maria Gabriela, Suco, Sofía, Vishnopolska, Sebastián Alexis, Berenstein, Ariel José, Jasper, Hector Guillermo, Domene, Horacio Mario, Rey, Rodolfo Alberto, Pérez Millán, Maria I., Camper, Sally, Bergadá, Ignacio
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/138682
Acesso em linha:http://hdl.handle.net/11336/138682
Access Level:Acceso aberto
Palavra-chave:Short Stature
GH1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Objective: to describe the marked variability in clinical and biochemical patterns that are associated with a p.R209H GH1 missense variant in a large Argentinean pedigree, which makes the diagnosis of GHD elusive. Design: We describe a non-consanguineous pedigree composed by several individuals with short stature, including 2 pediatric patients with typical diagnosis of isolated growth hormone deficiency (IGHD) and 4 other siblings with severe short stature, low serum IGF-1 and IGFBP-3, but normal stimulated GH levels, suggesting growth hormone insensitivity (GHI) in the latter group. Results: Patients with classical IGHD phenotype carried a heterozygous variant in GH1: c.626G>A (p.R209H). Data from the extended pedigree suggested GH1 as the initial candidate gene, which showed the same pathogenic heterozygous GH1 variant in the four siblings with short stature and a biochemical pattern of GHI. Conclusions: We suggest considering GH1 sequencing in children with short stature associated to low IGF-1 and IGFBP-3 serum levels, even in the context of normal response to growth hormone provocative testing (GHPT).

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